Experiences of consumers, carers and clinicians during borderline personality disorder presentations to the emergency department-An integrative review.

INTRODUCTION: People with a borderline personality disorder (BPD) diagnosis or symptoms may experience emotional crises which necessitate use of the emergency department (ED). No existing reviews focus specifically on experiences of consumersa, carersb and clinicians in relation to ED presentations by people diagnosed with BPD. AIM/QUESTION: The aim of this study was to synthesise knowledge on consumer, carer and clinician experiences of BPD in the ED. METHOD: An integrative review methodology was chosen as it best captures the complexity of varied perspectives and emergent phenomena from diverse literature sources. EMBASE, CINAHL, PsycInfo and Medline were searched for papers published before 16 February 2022. RESULTS: Nine papers met the inclusion criteria (five qualitative, one quantitative, one mixed methods and two letters to the editor). Key themes were barriers to timely and adequate care, and stigmatising attitudes and practices towards people diagnosed with BPD. Negative attitudes were perceived to perpetuate harmful outcomes and further ED visits. DISCUSSION: Predominantly negative ED experiences were expressed by clinicians, consumers and carers. Further work is needed in ED models of care and staff education to improve the experience of care for consumers, carers and clinicians alike. IMPLICATIONS FOR PRACTICE: Opportunities for change will exist through co-designed innovation, education, advocacy and leadership.

What clinicians need to know about intranasal esketamine for treatment-resistant depression?

OBJECTIVE: To review the usefulness of esketamine for treatment-resistant depression. METHOD: Pivotal trials of intranasal esketamine in treatment-resistant depression were synthesized as a narrative review. RESULTS: Esketamine is postulated to act through antagonism of N-methyl-D-aspartate (NMDA) glutamate receptors, but opioidergic effects may also be involved. Unlike intravenous ketamine, esketamine is given intranasally (under clinical observation), usually in addition to an oral antidepressant. Trials compared esketamine plus antidepressant versus placebo plus antidepressant. At 4 weeks, remission was 37% higher with esketamine/antidepressant than placebo/antidepressant. Speed of response and improvement in suicidality were comparable. In stable remitters on esketamine/antidepressant, 45% relapsed when esketamine was withdrawn over the following 6 months (whereas 25% relapsed on esketamine/antidepressant). Response appears less likely in patients with multiple antidepressant failures. Adverse effects include dissociation, dizziness, nausea, sedation, and headache but no psychosis. Hypertension affected 13%, especially older patients. Dose frequency is twice-weekly for 4 weeks, then weekly/fortnightly thereafter. No abuse has been reported. Unsubsidised cost may be beyond the reach of many Australians. CONCLUSION: Intranasal esketamine plus antidepressant has been approved by regulators as moderately effective and acceptably tolerable for treatment-resistant depression. Cost is a drawback. Use often needs to be long-term and vigilance for abuse is essential.

Mental Health Clinician Attitudes about Service User and Family Agency and Involvement in Recovery-Oriented Practice.

BACKGROUND: Recovery-oriented practice (ROP) is a framework focusing on recovery through hope, choice, and meaning, to live with or without enduring symptoms and challenges. AIMS: To examine clinicians' attitudes about the involvement of service users and family or supporters in ROP. METHODS: A bespoke Qualtrics survey obtained views of mental health clinicians working in an Australian public mental health service about service user and family involvement in ROP, using a five-point Likert scale of agreement and free-text responses. Data were analysed with descriptive statistics and content analysis methods. RESULTS: Two hundred and three clinicians completed the survey. Most (79%) clinicians agreed with the statement that service users want clinicians to use ROP principles, and the majority (63%) also 'strongly believed' that ROP made a difference to service users' mental health outcomes. Only 15% 'strongly agreed' and 57% somewhat agreed with the statement that service users know what treatment is best for them, and only 20% of clinicians 'strongly agreed' that supporters of service users believed in and wanted ROP for their family member or friend. FUTURE DIRECTIONS: This study adds to the literature on clinicians' views about ROP and shows that although clinicians are supportive of ROP, they also express substantial ambivalence about whether service users and families know what treatment is best. For ROP implementation to be successful, workforce training needs to support clinicians to reflect on these views with service users and families, and to encourage supported decision making. Future studies should focus on changes in clinicians' views and practice post ROP training.

Lemborexant, an orexin receptor antagonist sedative-hypnotic: Is it useful for insomnia in psychiatric disorders?

OBJECTIVE: Lemborexant, an orexin receptor antagonist similar to suvorexant, has been approved for the treatment of sleep onset and/or maintenance insomnia. Lemborexant is reviewed and compare to suvorexant from a psychiatric perspective. CONCLUSION: Rapidly absorbed (peak 1-3 h), lemborexant has a half-life of 17-19 h (suvorexant half-life 12 h). It is metabolized by CYP3A4/5, with no significant effects of age, sex or weight. Trials for insomnia indicate sustained efficacy beyond 6 months. Lemborexant has not been trialled in major psychiatric disorders. Commenced at 5 mg, lemborexant can then be increased to 10 mg, taken at least 7 h before planned awakening. Adverse effects are higher at 10 mg: somnolence occurs in about 10% while headache and nightmares affect 2-5%, approximately similar to 40 mg suvorexant (recommended suvorexant dose 20 mg). Sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms, complex sleep behaviours and emergence of depression/suicidal ideation can occur. Neither tolerance to sedation nor withdrawal effects on discontinuation have been observed. Whether the differences between lemborexant and suvorexant are clinically relevant is unclear. Like suvorexant, lemborexant appears to be effective in longer-term use for insomnia, but until efficacy and safety are adequately investigated in major mental disorders, clinicians need to monitor patient experience closely.

Cariprazine: A new partial dopamine agonist with a familiar profile.

OBJECTIVE: Cariprazine is the third partial dopamine agonist now available in Australia. This paper will review the properties, evidence and likely clinical place of cariprazine. CONCLUSION: Cariprazine is a partial agonist with high affinity at dopamine D2 and D3 receptors, partial agonism at 5HT1a receptors, moderate 5HT2a and H1 antagonism and no anticholinergic activity. It is rapidly absorbed, is unaffected by food, achieves a peak plasma level in 4-8 hours and has high bioavailability. The half-life of cariprazine and its metabolites is long (7-8 days); steady state occurs in 4-8 weeks. It is hepatically metabolized via 3A4 cytochrome enzymes. Cariprazine is an effective antipsychotic in acute schizophrenia in both short and longer placebo-controlled studies. Cariprazine appears to have small advantages in negative symptoms of schizophrenia. While not approved for bipolar disorder, cariprazine is effective in mania and mixed states but requires doses higher than current maximums recommended. Cariprazine causes more akathisia than aripiprazole or brexpiprazole but is less prone to insomnia, weight gain and sedation. Risks for hyperprolactinaemia and QTc prolongation are low. Cariprazine is another 'metabolically-friendly' antipsychotic for schizophrenia, with advantages for those with negative symptoms, mood symptoms or problems with adherence.

A critical review of the first six months of operation of a trial Hospital Outreach Post-suicidal Engagement (HOPE) service in Australia.

OBJECTIVE: To review the Hospital Outreach Post-suicidal Engagement (HOPE) service in the first six months of the pilot program in a metropolitan Melbourne setting, including a description of: (a) socio-demographic, health and psychosocial stressors of people referred; (b) method of presentation; (c) interventions provided and (d) outcomes measured. METHOD: A retrospective case file analysis reviewed the first six months of HOPE service operation. RESULTS: Forty people received HOPE service during the study period, 60% female, mean age 35 years (range 17-58). The majority had previously engaged in self-harm (72.5%) or attempted suicide (67.5%). Stressors included social isolation, relationship breakdown, unemployment, financial stress, medical problems, history of mental illness, exposure to family violence and adverse childhood events. Statistically significant improvements occurred in the Outcome Rating Scale (ORS) and Session Rating Scale (SRS) following intervention. There were no deaths by suicide during the study period. CONCLUSION: People referred to HOPE had significant health and psychosocial stressors. Engagement significantly improved subjective well-being and connection with supports. Findings highlighted the need for an integrated clinical and psychosocial model to promote hope and connection in life post suicide attempt. It remains unclear which interventions improved well-being and if this contributes to suicide prevention.

Engaging Healthcare Staff and Stakeholders in Healthcare Simulation Modeling to Better Translate Research Into Health Impact: A Systematic Review.

Objective: To identify processes to engage stakeholders in healthcare Simulation Modeling (SM), and the impacts of this engagement on model design, model implementation, and stakeholder participants. To investigate how engagement process may lead to specific impacts. Data Sources: English-language articles on health SM engaging stakeholders in the MEDLINE, EMBASE, Scopus, Web of Science and Business Source Complete databases published from inception to February 2020. Study Design: A systematic review of the literature based on a priori protocol and reported according to PRISMA guidelines. Extraction Methods: Eligible articles were SM studies with a health outcome which engaged stakeholders in model design. Data were extracted using a data extraction form adapted to be specific for stakeholder engagement in SM studies. Data were analyzed using summary statistics, deductive and inductive content analysis, and narrative synthesis. Principal Findings: Thirty-two articles met inclusion criteria. Processes used to engage stakeholders in healthcare SM are heterogenous and often based on intuition rather than clear methodological frameworks. These processes most commonly involve stakeholders across multiple SM stages via discussion/dialogue, interviews, workshops and meetings. Key reported impacts of stakeholder engagement included improved model quality/accuracy, implementation, and stakeholder decision-making. However, for all but four studies, these reports represented author perceptions rather than formal evaluations incorporating stakeholder perspectives. Possible process enablers of impact included the use of models as "boundary objects" and structured facilitation via storytelling to promote effective communication and mutual understanding between stakeholders and modelers. Conclusions: There is a large gap in the current literature of formal evaluation of SM stakeholder engagement, and a lack of consensus about the processes required for effective SM stakeholder engagement. The adoption and clear reporting of structured engagement and process evaluation methodologies/frameworks are required to advance the field and produce evidence of impact.

Stopping and switching antipsychotic drugs.

In general, specialist advice should be sought when stopping or switching antipsychotics While antipsychotics are often needed long term, there are circumstances when clinicians, patients and families should reconsider the benefits versus the harms of continuing treatment Withdrawal syndromes, relapse and rebound can occur if antipsychotics are discontinued, especially if they are stopped abruptly. Generally, they should be reduced and stopped slowly, ideally over weeks to months Relapse of psychosis and exacerbation occur in most patients with psychotic disorders, occasionally with drastic consequences. Sometimes this occurs many months after stopping antipsychotics Switching from one antipsychotic to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. It should be carried out cautiously and under close observation

Characteristics, diagnoses, illness course and risk profiles of inpatients admitted for at least 21 days to an Australian private psychiatric hospital.

OBJECTIVES:: To perform a clinical and risk audit of private hospital inpatients staying in hospital at least 21 days. METHODS:: Of 492 admissions for ≥21 days in 2016, 40 were randomly selected for audit. Characteristics, illness severity and course using the Clinical Global Impression severity (CGI-S) subscale and improvement (CGI-I) subscale, and clinical risk profiles were ascertained at admission, day 15 and discharge by two psychiatrists. RESULTS:: The cases were 65% female, age 50.0±16.2 years (range 24-86), 43% in relationships, and 28% on disability support. The length of stay was 29±7 days. On admission 88% were severely or markedly ill on the CGI-S subscale. Thirty-nine of 40 cases had ≥3 psychiatric diagnoses: 93% depression, 48% bipolar, 15% schizophrenia. High risk was present in suicide risk (48%), illness-induced dysfunction risk (78%) and physical risk (28%). By day 15, 63% were not improved or marginally worse. Suicide ratings were unimproved. By the time of discharge, illness severity and risk ratings were significantly reduced. CONCLUSION:: Private hospital inpatients staying ≥21 days were predominantly female and had severe, diagnostically complex illnesses and high risk ratings. Most were still seriously unwell after 15 days. Patients improved significantly by the time of discharge (though were by no means recovered), indicating that the duration of hospitalisation was appropriate.

Milnacipran: serotonin-noradrenaline reuptake inhibitor approved for fibromyalgia may be a useful antidepressant.

OBJECTIVE: Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) approved for treatment of fibromyalgia in Australia, but is used for depression in Europe and elsewhere. This paper will briefly review milnacipran and its utility in psychiatry for the treatment of depression. CONCLUSION: Milnacipran is a dual reuptake inhibitor of noradrenaline and serotonin, with greater effect on noradrenaline than serotonin, in contrast to the related drugs venlafaxine, desvenlafaxine and duloxetine. Rapidly absorbed irrespective of food, milnacipran has a half-life of approximately 8 hours, reaches steady state in 2 days and is excreted renally. Milnacipran helps a minority of patients with fibromyalgia by reducing pain and fatigue. It is also an effective antidepressant with efficacy comparable to venlafaxine and duloxetine, and a side effect profile characteristic of SNRIs. The dose range is 50-200 mg, in divided doses. Milnacipran may be useful for patients with depression and pain, and endogenous depression characterised by anergia, psychomotor retardation and hypersomnia. Caution is necessary in the presence of heart disease, hypertension, renal impairment, epilepsy, glaucoma, bipolar disorder, and bleeding tendency. Milnacipran is likely to be a useful late antidepressant option in treatment-resistant patients, as well as those with chronic pain, anergia and hypersomnia.

Brexpiprazole: a new leaf on the partial dopamine agonist branch.

OBJECTIVES: Brexpiprazole is a new dopamine partial agonist antipsychotic in the same class as aripiprazole. This paper will briefly review brexpiprazole and compare it with aripiprazole. CONCLUSIONS: Brexpiprazole and aripiprazole are both partial agonists at dopamine D2, and serotonin 5-HT1A and antagonists at serotonin 5-HT2A and noradrenergic α1B receptors. However, the two drugs are significantly different in potencies at various receptors; neurochemical profiles predict that brexpiprazole may be comparable with aripiprazole in its antipsychotic efficacy but may cause less akathisia, extrapyramidal side effects (EPS) and activation. In pivotal trials brexpiprazole demonstrated antipsychotic efficacy in short and long-term studies; it was also found to be an effective adjunct in patients with major depression resistant to antidepressants. Akathisia can occur early in treatment with brexpiprazole, as can minor weight gain and prolactin elevation. Indirect data extrapolations from pivotal studies suggest that brexpiprazole and aripiprazole have comparable efficacy but brexpiprazole may cause less akathisia. Like aripiprazole, brexpiprazole has been approved in the USA for use in schizophrenia and antidepressant-resistant depression. Although much more clinical experience is needed, brexpiprazole appears to be distinct from aripiprazole and a promising new 'metabolically-friendly' antipsychotic option for treatment of psychoses and mood disorders.

Suvorexant: scientifically interesting, utility uncertain.

OBJECTIVE: Suvorexant, a new hypnotic, is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance, and is used long-term. This paper will briefly review suvorexant. RESULTS: Orexin is a hypothalamic peptide which promotes wakefulness. By blocking orexin receptors, suvorexant induces sleep. Peaking 2 h after ingestion, it has a half-life of 12 h and is hepatically metabolized mainly by CYP3A. Kinetics are not affected by age but concentrations are higher in females and obese patients. There may be interactions with benzodiazepines, antidepressants and antipsychotics. Suvorexant is available in 15 mg and 20 mg doses at which benefits are moderate: after three months' treatment users fell asleep 6 min faster and slept 16 min longer than those on placebo. Studies with 40 mg showed greater benefits but more side effects: next day somnolence, fatigue, xerostomia and peripheral oedema. Hallucinations, sleep paralysis and somnambulism occur rarely. Tolerance, withdrawal and rebound do not generally occur at recommended doses. CONCLUSION: Suvorexant has not been trialled against other hypnotics, is expensive and its utility for insomnia in patients with psychiatric disorders is unknown. Currently, use of suvorexant could be considered where more established treatments are inappropriate.

Switching and stopping antidepressants.

Switching from one antidepressant to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. All antidepressant switches must be carried out cautiously and under close observation. Conservative switching strategies involve gradually tapering the first antidepressant followed by an adequate washout period before the new antidepressant is started. This can take a long time and include periods of no treatment with the risk of potentially life-threatening exacerbations of illness. Clinical expertise is needed for more rapid or cross-taper switching as drug toxicity, including serotonin syndrome, may result from inappropriate co-administration of antidepressants. Some antidepressants must not be combined. Antidepressants can cause withdrawal syndromes if discontinued abruptly after prolonged use. Relapse and exacerbation of depression can also occur. Gradual dose reduction over days to weeks reduces the risk and severity of complications.

Lurasidone: an antipsychotic with antidepressant effects in bipolar depression?

OBJECTIVE: Lurasidone is a new serotonin-dopamine antagonist atypical antipsychotic which also appears to be effective in bipolar depression. This paper will briefly review the evidence concerning lurasidone. CONCLUSIONS: Lurasidone is an antagonist at dopamine D2, serotonin 5-HT2 and 5-HT7, and partial agonist at 5HT1a receptors; it has no anticholinergic or antihistaminic activity. Rapidly absorbed, it has a half-life of 18 ± 7 hours, will reach steady state in five days and is taken at night with food (absorption is halved on an empty stomach). It is hepatically metabolised with some potential for interactions. Lurasidone is an effective antipsychotic in acute schizophrenia, and non-inferior to quetiapine but not risperidone in 12-month studies. Lurasidone may cause mild sedation, nausea, agitation, insomnia and akathisia (especially at initiation). Risks for weight gain, hyperprolactinaemia and QTc prolongation are low. Lurasidone has demonstrated antidepressant efficacy both as monotherapy and in addition to lithium or valproate in bipolar depression, of a comparable degree to that seen with the combination of olanzapine and fluoxetine. Lurasidone appears to be a "metabolically-friendly" antipsychotic for schizophrenia where weight gain and hyperprolactinaemia are of concern, and may also prove useful in bipolar depression (although not approved for this condition in Australia).

Should ketamine be used for the clinical treatment of depression?

OBJECTIVE: There has been widespread interest from the public and media in the potential of ketamine as a novel treatment for depression. This paper reviews whether current evidence supports the use of ketamine for the clinical treatment of depression. CONCLUSIONS: Clinical trials have investigated the use of intravenous ketamine for the treatment of depressive symptoms over the past 15 years. However, there remain many unanswered questions regarding its effectiveness, safety, and the route, dose and regimen for repeated administration. Experts have also raised concerns regarding ketamine's adverse effects, abuse potential and the risk of addiction. At this stage, the use of ketamine in the treatment of depression remains in the realm of research settings.

Aripiprazole long-acting injection: promising but more evidence needed.

OBJECTIVE: Aripiprazole long acting injection (ALAI) is now available, and this paper aims to assist clinicians in deciding when to use ALAI. CONCLUSION: Aripiprazole is a partial dopamine agonist with low sedation, relatively favourable metabolic profile and a tendency to lower, rather than raise, prolactin. Available for over a decade, aripiprazole has been increasingly recognised by many clinicians as a useful option in the treatment of psychoses. ALAI is a suspension of crystalline aripiprazole in water which takes 5-7 days to reach steady state after an initial intramuscular injection. Monthly injections achieve steady state in four months. Studies have demonstrated that ALAI is effective in aripiprazole-responsive patients. ALAI was generally well tolerated, but more prone to cause extrapyramidal side-effects than the oral form. ALAI has not been compared with other depots. Although the recommended starting dose is 400 mg, it is likely that there will be significant inter-individual dose variation. Dose optimisation in each patient will be necessary for best effectiveness and tolerability. ALAI is currently appropriate for aripiprazole-responsive patients who need a depot, but clinicians are likely to try ALAI in patients who have been on other depots, particularly in whom weight gain and hyperprolactinaemia have been problematic.

Vortioxetine: A multimodal antidepressant or another selective serotonin reuptake inhibitor?

OBJECTIVE: The treatment of depressive disorders remains unsatisfactory for many patients with regard to efficacy and tolerability. Vortioxetine has been registered by regulatory authorities for the treatment of major depressive disorder. This paper aims to provide clinicians with a brief overview of vortioxetine and its place in treatment. CONCLUSIONS: Vortioxetine is a serotonin reuptake inhibitor with additional serotonergic receptor effects of uncertain significance; hence, its classification as 'multimodal'. The half-life is about 2.75 days and steady state requires about 14 days. Metabolism is hepatic and involves cytochromes 2D6 and 3A4/5. Antidepressant efficacy in major depressive disorder has been established in registration studies, but the effectiveness of vortioxetine in 'real world' patients and in comparison to other antidepressants needs further investigation. The recommended dose range is 5-20 mg. Nausea, constipation and vomiting are the most common side effects. Sexual dysfunction may occur at higher doses but there appears to be low risk of weight gain and sedation. There is still much to learn about this drug, particularly whether it has unique characteristics in comparison to existing antidepressants. At present, vortioxetine can be considered as an antidepressant option in patients with established major depressive disorder who have not responded adequately to other antidepressants.

Management of antidepressant-induced sexual dysfunction.

OBJECTIVE: Antidepressant-induced sexual dysfunction is a common, troublesome complication of antidepressant treatment that patients often fail to report, which can have major consequences, including non-adherence to treatment with resultant relapse of depressive illness. The aim of this paper is to review the extent, causation and evidence-based management of antidepressant-induced sexual dysfunction to inform clinical practice. CONCLUSIONS: The preponderance of evidence suggests that antidepressant s can be divided into high risk (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors) and low risk (agomelatine, bupropion, moclobemide and reboxetine) categories with regard to propensity for antidepressant-induced sexual dysfunction, although there is disagreement, particularly about mirtazapine, and methodological issues militate against definitive findings. Antidepressant-induced sexual dysfunction is dose-dependent to an extent, but patient vulnerability factors are also relevant. There are significant differences in antidepressant-induced sexual dysfunction between men and women. It is important to ask antidepressant -treated patients about sexual dysfunction as few self-report; this may well contribute to antidepressant non-adherence. Consider using an antidepressant with low risk of antidepressant-induced sexual dysfunction for initial treatment. When antidepressant-induced sexual dysfunction has developed, try to persuade the patient to wait in case tolerance develops. Then consider changing to a lower risk or use of high/low risk antidepressant combinations but pharmacological expertise is required. Adjunctive sildenafil can help in both sexes.

Quality of life in schizophrenia: a review of the literature from 1995 to 2000.

The measurement of the quality of life of patients diagnosed with psychiatric disorders has become central to evaluating the effectiveness of treatments offered by Australian mental health services. The importance of quality of life as an indicator of the outcomes of interventions has been reflected by a large body of research seeking to measure the impact of variables such as gender, ethnicity and duration of illness on the measurable quality of life of an individual diagnosed with schizophrenia. This study aims to review and synthesize the recent literature in which quality of life has been measured by the use of at least one quality of life instrument. It is concludes that while the measurement of quality of life is valuable as a measure of outcomes, it should be treated as only one means of doing so.